Dr. Kevin Hall — Dueling Diets

>> Diego (narration): Well, if you can believe it, it’s already March, which marks a year since the first lock down orders were put in place here in the US. For most of us that means a full year of limited social interaction. For me, that’s meant more nights than I care to count in sweat pants, TV remote in one hand and the other wrist-deep in a bag of potato chips—or whatever the junk food du jour might be.

In adhering to CDC guidelines, many people have reduced the time they spent outside of their homes and perhaps noticed that their waistlines haven’t necessarily adhered to what they used to be pre-pandemic. It’s what the internet is now calling the quarantine fifteen—clever, if it weren’t so harsh. Personally, I don’t think there’s any shame in packing on a few pounds, especially considering everything that’s happened over the last twelve months. But if you are trying to pick up healthier eating habits, it’s difficult to figure out exactly what do to.

When walking the aisles of a grocery store, knowing what items to put in your shopping cart might feel a little overwhelming. There are so many food options! And it doesn’t help having vague recollections of the food fads from social media or TV commercials contradicting each other in your head. One day eggs are good for you, the next they have too much cholesterol. You want to lose weight? Cut out all fats. But what about the keto craze? Doesn’t it say you should eat mostly fats?

Nutrition is a contentious topic. It’s hard to tell fact from fiction. Fortunately, there are scientist like Dr. Kevin Hall who are working to debunk the myths and give us the real skinny on how the foods we eat affect our health.

Dr. Hall is a senior investigator and the chief of the Integrative Physiology Section at the National Institute of Diabetes and Digestive and Kidney Disease. His research looks at how our bodies and brains respond to different diets and levels of physical activity. For example, in a study published in 2016, Dr. Hall reported that six years after being on The Biggest Loser—the popular weight loss TV show— the contestants regained about two-thirds of the weight they had lost, and their metabolisms had persistently slowed down. Surprisingly, their bodies were burning fewer calories in what seemed like an attempt to counter the participants best efforts to keep the weight off.

This year, Dr. Hall and his collaborators published a study that put two well-known diets head-to-head to see which led people to consume more calories. I had a chance to catch up with Dr. Hall and get the scoop on what he found

>> Diego (interview): Thank you for being here Dr. Hall, even if it can only be virtually.

>> Dr. Hall: My pleasure:

>> Diego (interview): Well, I kind of just want to jump straight into your new study that was published in Nature Medicine this year. In it, you brought 20 subjects, 11 men and 9 women, to the NIH Clinical Center's Metabolic Clinic Research Unit, where you basically gave one half of the group a plant-based, low-fat diet, and the other half an animal-based low-carbohydrate diet. And then after two weeks, you switched the diets so that those on the low-fat regimen started eating low-carb and vice versa. So, can you walk me through what you were looking for and what you found?

>> Dr. Hall: Yeah, absolutely. So that's an accurate description of the study design. I think the added important message is that this was not a weight loss study. So, a lot of people think of these diets in terms of weight loss. But we were interested in trying to understand the factors in different diets that contribute to how much people consume, how much food do they consume in terms of calories per day. So, we've been very interested in our lab over the years trying to understand how does the body adapts the fuels that are being used to basically perform the kinds of things that we do from a day-to-day basis, both physical activity as well as when we're just resting. You know, our cells require energy to kind of maintain ionic gradients, to do their functions, all of those kinds of things. And so, the fuel that we use in order to perform those functions essentially come from carbohydrate, fat, and protein.

>> Diego (interview): Before you go on, can you recap what the differences are in the way our bodies use those different types of food for energy?

>> Dr. Hall: Yeah, so the idea is that the body uses these three different macronutrients, carbohydrate, fat, and protein in order to fuel our metabolism. It basically burns whatever you give it, essentially. And it happens quite quickly. So, for example, in this diet, the protein amount was kept constant that we were providing to people. But we had these huge differences in carbohydrate and fat with the low-carb diet being only 10% carbs and 75% of calories from fat, and the low-fat diet being only 10% fat and 75% of calories from carbs. So, the fuels that are being put into the body are very different in these two cases. And yet, the body does a really good job of switching in a sort of flex-fuel vehicle type manner of “okay, well we see we're getting a lot of gasoline one day, or i.e. a lot of carbs, then we can switch to burning those carbs.” Whereas if we're now cut off on carbs and we're getting a lot of fat, well we can adapt quite quickly and burn a lot of fat or diesel, as the analogy might be. And perform its normal metabolic functions as a result of those switches in fuels. This study showed those kinds of adaptations as well. We very clearly saw it. But what we were more interested in was whether or not these kinds of diets would change people's appetite overall, would cause them to eat more or eat less, and that was the primary objective of this study. Because we were actually trying to test a couple different theories about why people overeat and become obese.

>> Diego (interview): Can you tell me a little bit about those theories?

>> Dr. Hall: Yeah, sure. So, there’s been a couple of –well, there's been many different theories about what it is about our food environment that causes people to overeat and gain weight. One was that if you eat too much fat in your diet, because fat has many more calories per gram, consuming the same amount of food will result in a greater calorie intake and therefore you'll have a tendency to gain weight.

>> Diego (interview): So that’s essentially saying, food that's higher in fat is denser in calories. So, like if you eat the same volume of something that's high in fat versus high in carbs, you're more likely to get more calories.

>> Dr. Hall: Yeah, that's exactly right. For every bite that you take, essentially, you'll be consuming more calories. And so that was something called the passive over-consumption model of obesity. In contrast, one of the theories about why sugar and carbs or even just starches and high glycemic index foods might lead to obesity is something called the carbohydrate insulin model of obesity. And the idea there is pretty interesting. It basically says if you want to understand how people get fat, you have to understand how fat cells get fat. And one of the things that we know about fat cells is that a hormone called insulin plays a major role in regulating whether or not fat is being released from fat cells into the circulation or being taken up and stored inside fat cells. So insulin plays a reatlly important role. Well, what determines how much insulin is secreted? It turns out that carbohydrates in the diet are one of the primary determinants of insulin levels after eating meals. So, if you eat a high-carb meal, especially one that has a lot of high glycemic carbohydrates like sugar, or you know, white bread, or a potato, or something like that, then you will tend to have a very large spike in insulin secretion. Which then drives the fat into the fat cell and keeps it there, essentially, is the idea. And the carbohydrate insulin model then goes onto say well if you're diverting all of these calories into fat cells because insulin levels go up so high, maybe other tissues like your muscles or your liver are now sensing less fuel available to them. And that will somehow signal to the brain to be hungrier. And this is what they explain as, you know, the reason why if you eat a very high carb meal, you know, three or four hours after eating, you're probably even hungrier than you were to begin with.

>> Diego (interview): Yeah, I can attest to that, that's true.

>> Dr. Hall: Yeah. So, that's the idea. And so therefore, you know, if you eat a high glycemic index diet and you kind of have these large spikes in insulin, the carbohydrate insulin model would predict that you will eat more calories and gain weight and gain body fat. And so that's what we did in this study. We designed two diets that were matched for protein but have very different amounts of carbs and fat. The low-fat, high-carb diet had a much higher glycemic load, and in fact caused much higher increases in insulin. The low-carb, high-fat diet was higher in calorie density. In other words, more calories per gram—more calorie per bite. And so, we were putting these two models of obesity head-to-head in this study.

>> Diego (interview): This low-carb diet that you provided is very similar to what a lot of people might recognize as the ketogenic or the keto diet. Essentially, eating foods in high-fat, like avocados, eggs, cheese. And I know that the jury's still out on whether keto is king. Some people experience great success on it, others not so much, it's not, you know, it doesn't work for everyone. But from what you're telling me, it sounds like the ketogenic diet corresponds to the carbohydrate insulin model?

>> Dr. Hall: So yeah, a couple things. I think we should be maybe a little bit more clear about the diets. So what we did was we decided we want to have kind of these extreme diets. The very low carb, you eat 10% or so carb, very high fat, which is what you're calling the keto diet, which is correct. Versus the very low-fat, high carb diet. And we wanted to make them kind of the best versions of both of those diets that we could. So we didn't want to kind of bias the study in one direction or another just because we were providing people with either, you know, super tasty foods on one and really bland or unfamiliar foods on the other. But the basis of both of them is a whole bunch of non-starchy vegetables. Things like, you know, peppers and all the green leafy vegetables that most people think of. And then for the keto diet, as you say, there's a lot of animal-based products, like eggs and fish and beef and cheese. And a bunch of other dairy products. And so what we did was we added those animal based products to kind of get to the desired goal of the 10% carbs, 75% fat, 15% protein.

And then the other side, even though low-fat diets have kind of fallen out of favor in much of the world, for weight loss and things like that, there is a group of people who still recommend very low-fat diets. And they happen to be vegans. And so we decided to make it ecologically relevant, we would say okay, well let's design the very low-fat diet based on the group of folks who advocate for those kinds of diets currently. And they tend to be whole food, plant-based vegan diets. And so that diet gets 100% of the calories from plant-based foods. It has no animal-based products. And then is designed to have a lot of starchy vegetables, which contribute a lot to glycemic load, which allowed us to have much higher insulin levels after meals. In fact, the insulin differences after meals were threefold higher with the low-fat, high carb diet compared to the ketogenic diet. And in fact, over the course of the day, insulin secretion was 60% higher. So, we clearly got the differences in insulin that would have been predicted by the carb insulin model to kind of drive the fat cells to go into storage mode and therefore gain fat. But we still didn't see that. In fact, the only diet that ended up with people losing fat was the low-fat diet. Not the low-carb diet. In our study.

>> Diego (interview): I see. Interesting. But like you said weight loss wasn’t the main objective of the study. You we’re focused on calorie intake. So, what did you find there?

>> Dr. Hall: Right. So, the same people, these men and women, with a wide range of body mass indices, so they range from like 18 to 40, think, which is kind of going from like very lean to class three obesity. They consumed on average almost 700 calories a day less on the low-fat diet compared to the low-carb diet. Which is completely opposite to the prediction of the carbohydrate insulin model. But the other important point was that even though people were consuming about 700 calories per day more on the low-carb, high-fat diet, we didn't interpret that as support for the passive overconsumption model.

>> Diego (interview): Really? Why is that?

>> Dr. Hall: Because people didn't gain body fat. Right? And you would expect that if they're eating so much fat, which is much higher than is typical for a person and a very high energy density, calorie density, in other words calories per gram or per bite for food that you think about, the passive overconsumption model would predict that people should overeat and gain weight and gain body fat. And that did not happen. So, our conclusion was, you know, we can sort of rule out, the carbohydrate insulin model predictions because they went in the opposite direction. But we can't actually say that this supports the passive overconsumption model, either. In other words, what determines whether people overeat and consume more calories and gain more weight and gain body fat is more complicated than either of those two models proposed.

>> Diego (interview): Right, sure. It really seems that this is all a little bit more complex than just overeating and weight gain due to the amount of carbs or fat in a person's diet. And you kind of investigated other variables in this puzzle, namely the impact of ultra-processed foods on weight gain. Can you talk a little bit about that work? Maybe starting with what falls under the category of processed food?

>> Dr. Hall: Yeah, sure. So there's this concept that, overeating and health, in fact, when it comes to dietary determinants of health, have very little to do with the composition of the diets in terms of macronutrients; the carbs, fat, and protein. Maybe it's a broader kind of holistic idea. And so there's a group of people who started out in Brazil who basically said, “no, no, no, you've been looking at nutrition all wrong for the past, you know, century or so. It's not about the individual nutrients that are in foods. That's not really that important. What's important is the degree and extent to which the foods that we eat have been processed. And the purpose of that processing.” And it's a pretty radical idea I would say. And I don't fully believe it. In fact, I didn't believe that there was anything to it when I first read about this. I'm actually a physicist by training, I have no formal nutrition, so I'm a reductionist. I like the idea that you could just take a food apart in terms of its nutrient constituents and understand its behavior in the body based on those nutrients. And these guys come along, and they say no, no, no, it's not about nutrients. It's about the purpose and extent of the processing of the foods. And so they came up with this alternative universe, where they say I don't care how much carbs are in the foods, I don't care how much fat, I don't care how much saturated fat. We're just going to categorize foods according to four different classifications. One is basically unprocessed or minimally processed foods. Where it's like eating a raw apple, right? You're allowed to wash it, you're allowed to cut it up—and that's processing, per se, so that's a semantic argument. But even things that you cook in a normal way, like if you boil a potato or something like that, that’s all minimally processed food. So that's category 1.

Category 2 is what they call culinary ingredients. Things like sugar, butter, olive oil, things that you don't eat alone but you combine with category 1 foods to cook and prepare meals.

Category 3 are basically the combinations of category 1 and category 2 foods. It's what they call processed foods. It's what a lot of us would call meals. Right? You combine those two things, it's a meal. You can do that, you could also do that in an industrial way, right? In your supermarket you can find prepared meals that are essentially category 3 processed, but they're essentially combinations of category 1 and category 2 foods. So all of those three categories of foods, according to these folks, get the thumbs up. It's okay. Eat as much or as little as you want of all of those things.

>> Diego (interview): Whew. Okay, good. Otherwise, I wouldn’t know what to eat.

>> Dr. Hall: So then they identify this other group, which they call the ultra-processed group. Which is a bit of a-- you know, in my opinion, it's a bit of a squishy definition. But it's essentially, you know, do the foods contain ingredients that are not generally available for common cooking? You know, things like emulsifiers or flavor additives or color.

>> Diego (interview): Yeah. That's what I think of when I think of processed foods.

>> Dr. Hall: Right. And the way they—they have a couple different definitions. You know, some preservatives and things like that might be there. Even fortification with vitamins kind of moves some things into the ultra-processed category. And they define this, I don't have the definition in front of me, but it's something along the lines of that these foods are kind of made with cheap sort of agricultural inputs like corn and soy products that basically form these kind of foods that you can't identify the original whole foods that were used to produce them. So think of a corn chip. You can't find any corn in a corn chip, right? Or a potato chip. It kind of looks like a potato, but it's not—you know, a lot of the stuff in the middle of the supermarket, is ultra-processed. Again, it's one of those things that from a scientific perspective, it's not very satisfying as a definition of a food category. But it’s what the author Michael Pollan calls "food-like substances." Right? It's-- he doesn't even define it as food, it's kind of like these food-like things that are not, they're not real food in his view.

>> Diego (interview): And you found that these not-so-real foods essentially are a huge factor in weight gain, though, right?

>> Dr. Hall: Right. So, I think it's important to kind of put that study in the context of the study we've just published. So in the study we've just published, one diet was very low in carbs and high in fat and had very many calories per gram. In the previous study, we had one diet that had an equivalent number of calories per gram in the foods, but it derived 80% calories from ultra-processed foods, that category 4 foods. That diet led to weight gain, overeating, and fat gain, body fat gain.

So, one interpretation would be well if calorie density was the only thing that mattered, then why was it that two diets that were matched for calorie density, only one of them led to weight gain and body fat gain, whereas the other one did not?

>> Diego (interview): Right.

>> Dr. Hall: So these two studies I think tell us that what regulates people's appetite and how much they decide to eat is there's no one single factor that seems to explain all of these data. We think that it's probably some combination of the calorie density. We think it might also be something about the ultra-processed foods that are in the diet over and above their impact on calorie density that cause people to overeat and gain weight. So it's really darn complicated. And so our goal over the next, you know, who knows? Decade, I would guess. Is to kind of figure out the relative importance of these different factors in our food environment that determine human appetite regulation. You know, how much people want to eat. And understand hopefully, you know, what are the factors in the food environment that contribute to overeating and weight gain. And what can we do to kind of mitigate those factors.

>> Diego (interview): Right. Well this kind of speaks to something that I saw in my research preparing to talk to you. It seems like nutritional science can be a little bit contentious. Not only the findings that you're talking about, but like some people swear by a certain diet or a certain fad as like the holy grail of health. And I assume you face some pushback from people when you publish new findings that might contradict those earnest beliefs in, you know, eating a particular way. Especially with, you know, the attention food gets in the popular press, and with the accessibility of social media. So how do you deal with that criticism as a scientist?

>> Dr. Hall: It's been interesting. I mean like I said, I was not trained in this particular area of research formally. And you know, while I thought that the kind of research, I did previously was important, nobody had an opinion about it, right? No one had an opinion about, you know, what really causes atrial fibrillation is this--

>> Diego (interview): Right, that usually flies under the radar.

>> Dr. Hall: Right. And so, I think that people oftentimes misinterpret our studies as saying something more than they actually are intended. So for example in this latest study with low-carb versus low-fat diets, I'm trying to be very clear. This was not a weight loss study.

This is a study designed to understand how when you expose people to very different food environments with very different kinds of dietary patterns, how does that influence their spontaneous calorie intake over, you know, pretty substantial durations. A couple weeks at a time, right. So, it's not like people can game the system. They could game the system for a single meal, right. But to game your appetite over two continuous weeks is kind of hard. So, we think we're actually seeing something real. And especially when we blind the subjects to what we're actually primarily interested in. So, whether or not we would get the same result if we said okay, we're going to bring in a bunch of people with overweight and obesity and we're going to call this a weight loss study, and we're going to randomize you to two different diets for weight loss, it's a very different impression about what's going on, right? Because now it's like oh, everybody knows that you have to kind of cut back on something to lose weight, right? Whether or not we would have seen anything like the results that we saw under that kind of scenario is a completely open question. And what determines whether or not somebody is successful or not is at this point completely unknown. And of course, there's a lot of work going on to try to look at precision nutrition to identify what person should be prescribed what diet based on their genes or based on their physiology or something else. But it could also be, you know, people's social situation that may determine whether or not they were successful or not. It could be that the person who was very successful when they were prescribed a low-carb diet would have been equally successful if they'd been prescribed the low-fat diet. They happen to be at the right time in their life, they have a supportive partner that allowed them to make a lifestyle change that was meaningful. It might have nothing to do with biology. Which is kind of frustrating. We don't know the answer to that question yet.

>> Diego (interview): Yeah, that's all so complicated, like you said. It's different in the lab and in the real world. And like I'm assuming it's very frustrating who've been trying, you know, different diets and all that stuff to not know exactly what is most beneficial.

>> Dr. Hall: Well, it doesn't help that, you know, like you said, there's a lot of interest in this area. And there's so many claims. Which I think are, you know, more or less unfounded. And a lot of compelling narratives. Right? So, we talked about two what I thought were pretty compelling narratives. This carbohydrate insulin model of obesity idea; if that's true, you know, the solution is quite straightforward, right? Just cut carbs and keep insulin levels low after meals. Which we were able to do very straightforwardly in our experiment. But it turns out that it's not that simple. But it sounds very scientific, and it has a genuine scientific basis. And when you kind of write a diet book based on this idea and you have a compelling storyteller telling that story, and also telling them, you know, the reasons you may have failed on a diet in the past are not your fault—and that’s probably true, it's not their fault—now you'll be successful because we finally understand the reason. Well, the problem is that we might not yet really understand the reason. And it's maybe a little bit more complicated than is being proposed. And if all of that stayed in the scientific community and there were debates about this and you know, it wouldn't really impact the public too much. But I think what happens is that people have these compelling narratives, and they feel the need to kind of get out there in front of the public and tell them this is the real cause of obesity. But it's too simple, in my view, at least, to explain what's going on. And therefore, people get confused because it competes with another seemingly, you know, compelling narrative based on some science. And it turns out real life and real biology and real physiology is more complicated than any of these relatively simplistic narratives.

>> Diego (interview): Right. And that's exactly why we need people like you to keep working that it and actually find something that's a little bit more concrete for people to follow.

>> Dr. Hall: Well, hopefully we'll have some concrete answers in the future. Right now, we seem to be doing more practical debunking than anything else.

>> Diego (interview): Well, you said that you're obviously trained as a physicist. How did you end up in nutritional science? Did you always intend to go in this kind of route?

>> Dr. Hall: Yeah, not at all. It's kind of a complete accident in some way. So, I did my undergraduate degree in physics. Sort of realized I wasn't good enough at mathematics to go into the kind of theoretical particle physics that I was interested in. And so, I started to look around at other things. And I got interested in mathematical biology. And I went to a very unique place for graduate school at McGill University called the Center for Nonlinear Dynamics and Physiology in Medicine. I could have gone into the physiology department, but I didn't want to write a comprehensive exam in physiology. So, I decided to stick in the physics department. But I was making mathematical models of different kinds of heart rhythms and trying to analyze the dynamics of different kinds of transitions between different kinds of cardiac arrhythmia. And then I decided after my PhD that I didn't want to do a post-doc. But there was a little company in the San Francisco Bay Area that was forming called Intelos. And they were building different mathematical models and computer simulations of diseases in collaboration with pharma. And so they hired me and said you're in charge of our type 2 diabetes program. And I said what's type 2 diabetes? But over the next four years, I learned a lot about nutrition and metabolism and endocrinology. We worked with a variety of big pharma partners to develop a pretty interesting computer simulation model of the underlying physiology of carbohydrate, fat, and protein metabolism. And glucose regulation. And I was fortunate to work with some very well-known consultants. Because I was there for four years, didn't publish a single paper. And there was a tenure track position open at NIDDK. And I was fortunate to have some very high-profile people write me good letters of recommendation and fortunately then this scientific director of NIDDK was-- took a risk basically on this kid who hadn't published anything in four years. Had a few pretty good papers in his PhD on a completely different topic.

>> Diego (interview): Yeah.

>> Dr. Hall: But that's when I started my lab at NIDDK. And I was just doing computer simulation models for the first few years in the tenure track. And I gave a presentation, and the clinical director said hey, that was an interesting prediction of your model, have you ever decided to try to test it? And I'm like it's a human model, how am I going to test it? And like well, learn how to write a protocol. And learn how to do this. And I said sure. Why not? What could go wrong? I'll design a human clinical research study and hire a couple of people to help me do that. And that's what I did. And so we started our first human study in 2009. And it took us, I guess, several years to kind of get 19 people through the program. Because it was basically me, a post-doc, and a post-baccalaureate fellow running the study. And then those two people were rotating in and out. And it took us forever to kind of do the first study. But it turned out pretty well. And it validated our model prediction. And so now we sort of have these two parallel arms going, the vast majority of our studies are clinical research at the clinical center. And the minority is still developing these mathematical models of human metabolism.

>> Diego (interview): Got'cha. And is the idea to validate the mathematic models with the clinical ones? Do they go hand-in-hand?

>> Dr. Hall: They go hand-in-hand, yeah. For the most part, actually. But the one exception was the ultra-processed food study. Our model says absolutely nothing about ultra-processed food, which was why I was expecting there to be absolutely no difference between the two diets. And yet we saw this huge difference. I’m like well our model doesn't really address it, so it's not wrong, it's just incomplete. But yeah, the idea is that we can use our data to kind of help improve our model and basically show us where we're wrong. And the model is kind of useful for helping design the experiments and predicting, you know, what might happen to the body weight and body fat on these different diets and things like that.

>> Diego (interview): Got'cha. Well, thank you. All this talk of food has made pretty hungry for lunch. But you gave me a lot to chew on, so I appreciate it.

>> Dr. Hall: That's great, thanks.